Yeast Builds Better Monoclonal Antibodies

Proteins help the immune system recognize bad cells and neutralize them. Immune cells produce such proteins, or antibodies, in a variety of types and structures, only some of which target a specific disease producer, whether it is virus, bacteria, cancer or something else entirely. By isolating the immune cells that produce a specific antibody, scientists can create monoclonal antibodies--a concentrated dose of a specific disease targeting protein. Thus far, researchers have relied on the cells of other animals, such as Chinese hamsters, to produce these powerful medicines. Now new research suggests that yeast can be engineered to produce even more effective antibodies.

The key is sugar. When produced by animal cells, monoclonal antibodies have slight variations in some of their internal sugars. Previous research showed that these slight variations could cause the immune system to pass up the opportunity to neutralize the bad cell the antibody had identified by binding to it. Huijuan Li of GlycoFi and her team created a strain of ordinary yeast that produced monoclonal antibodies that perfectly matched the human sugar structures. These yeast-produced antibodies proved 10 times more effective than animal-derived antibodies in binding to the bad cells in vitro. "By controlling the sugar structures on antibodies we have shown that the antibodies' ability to kill cancer cells can be significantly improved and that therapeutic proteins can be optimized," Li says.

GlycoFi, a biotechnology company, hopes to mass produce such proteins from yeast in the future, citing lower costs and a longer history of such production. They also argue that because the yeast-produced antibodies can be engineered to closely match human antibodies, they could be used to optimize characteristics such as solubility, duration of the medical benefit, distribution in the body and interactions with other proteins. Although such claims remain to be tested, the yeast antibodies have showed improvements already in spurring the immune system to get rid of cancer cells during additional in vitro testing. The findings were published online yesterday by the journal Nature Biotechnology.